HMGA1

HMGA1 is a human gene that encodes the high mobility group AT-hook 1 (HMGA1) protein, a small non-histone chromatin-binding protein involved in the regulation of transcription and chromatin architecture. HMGA1 proteins bind to AT-rich DNA sequences in the minor groove through three DNA-binding motifs known as AT hooks, and they feature an acidic C-terminal tail. Two major isoforms, HMGA1a and HMGA1b, arise from alternative splicing of the transcript.

As an architectural transcription factor, HMGA1 does not typically activate transcription directly but modulates the structure of chromatin and facilitates the assembly of transcriptional regulatory complexes. Through these actions, HMGA1 can influence the expression of a broad set of genes involved in development, cell proliferation, differentiation, and inflammatory responses. It is expressed at high levels in embryonic tissues and can be re-expressed in adult tissues under certain physiological or pathological conditions.

Dysregulation of HMGA1 has been linked to disease. In cancer, HMGA1 is frequently overexpressed and is associated with increased tumor growth, invasiveness, and poor prognosis in several tumor types. Its role in cancer is attributed to chromatin remodeling that enables activation of oncogenic pathways and genes. HMGA1 is also studied in the context of development and metabolism, as research suggests it can influence signaling pathways related to insulin and glucose regulation.

Overall, HMGA1 serves as a component of the chromatin regulatory machinery, altering DNA topology to modulate gene expression and participate in diverse biological processes.